Combinations of pyrimethanil and silver compounds

ABSTRACT

The present invention relates to combinations of pyrimethanil, or a salt thereof, and silver compounds which provide an improved biocidal effect. More particularly, the present invention relates to compositions comprising a combination of pyrimethanil, or a salt thereof, together with one or more silver salts selected from silver acetate, silver alginate, silver azide, silver citrate, silver lactate, silver nitrate, silver sulfate, silver chloride, silver thiocyanate, silver-sodium-hydrogen-zirconium phosphate, silver sulfadiazine, silver cyclohexanediacetic acid and disilver 2,5-dichloro-3,6-dihydroxy-2,5-cyclohexadiene-1,4-dione; in respective proportions to provide a synergistic biocidal effect. Other suitable silver components (II) are products that set silver free using technologies to make it gradually biologically available such as by ion exchange mechanisms such like using zirconium phosphate based ceramics as a reservoir, or silver provided in glass ceramics as reservoir or carrier, or silver provided with zeolites, silica gel or titanium dioxide as a reservoir or an inorganic derivative containing silver, incorporated into a plastic composition for the preparation of moulded, lacquered or painted products, such as an amino resin (e.g. urea-formaldehyde resin, melamine formaldehyde resin . . . ) or a thermoplastic (e.g. a polyester, polyethylene, polyacrylate, pvc . . . ), or provided as nano-silver particles typically with a particle size of 1-1000 nm. Compositions comprising these combinations are useful for the protection of any living or non-living material, such as crops, plants, fruits, seeds, objects made of wood, thatch or the like, biodegradable material and textiles against deterioration due to the action of microorganisms such as bacteria, fungi, yeasts, algae, and the like.

The present invention relates to combinations of pyrimethanil, or a saltthereof, and silver compounds which provide an improved biocidal effect.More particularly, the present invention relates to compositionscomprising a combination of pyrimethanil, or a salt thereof, togetherwith one or more silver salts selected from silver acetate, silveralginate, silver azide, silver citrate, silver lactate, silver nitrate,silver perchlorate, silver sulfate, silver chloride, silver thiocyanate,silver-sodium-hydrogen-zirconium phosphate, silver sulfadiazine, silvercyclohexanediacetic acid and disilver2,5-dichloro-3,6-dihydroxy-2,5-cyclohexadiene-1,4-dione in respectiveproportions to provide a synergistic biocidal effect. Compositionscomprising these combinations are useful for the protection of anyliving or non-living material, such as crops, plants, fruits, seeds,objects made of wood, thatch or the like, engineering material,biodegradable material and textiles against deterioration due to theaction of microorganisms such as bacteria, fungi, yeasts, algae,virusses, and the like.

Microorganisms are extremely useful, and even indispensable, inprocesses such as, e.g. alcoholic fermentation, ripening of cheese,baking of bread, production of penicillin, purification of waste water,production of biogas, and the like. However, microorganisms can also beharmful or highly dangerous; by causing infectious diseases, by formingpoisonous or carcinogenic metabolites and by attacking valuablematerials, disturbing production processes, or impairment of the qualityof products.

Biocides or microbiocides are a broad and diverse group of compoundswhich are able to control microorganisms: i.e. to eliminate, kill, orinhibit microorganisms, or to reduce the growth or proliferation ofmicroorganisms such as bacteria, fungi, yeasts and algae. An importantgroup of the biocides are the bactericides and fungicides. Sincebacteria and fungi occur everywhere, their destructive activity(biodeterioration) is basically unavoidable. Nevertheless objects can beprotected with the aid of compounds that prevent the multiplication ofbacteria or fungi at the relevant sites, either by killing them orinhibiting their development.

Fungicidal combinations comprising the antifungal agents pyrimethaniland imazalil have been disclosed in WO-2003/011030. WO-2006/045751discloses the use of the pyrimethanil, cyprodinil and mepanipyrim forthe protection of wood and wood materials against wood destroying andwood discolouring fungi.

US-2006/0086283 discloses the use of silver, in the form of silvernitrate, as a biocide in a wood preservative product. And WO-2006/047126discloses wood preservative compositions present as micronized particlescomprising metal inorganic components, such as silver, and organicbiocides.

It has now been found that the combination of pyrimethanil (hereinafterreferred to as component I) and one or more silver compounds selectedfrom silver acetate, silver alginate, silver azide, silver citrate,silver lactate, silver nitrate, silver perchlorate, silver sulfate,silver chloride, silver thiocyanate, silver-sodium-hydrogen-zirconiumphosphate, silver sulfadiazine, silver cyclohexanediacetic acid anddisilver 2,5-dichloro-3,6-dihydroxy-2,5-cyclohexadiene-1,4-dione, has asynergistic effect on the control of microorganisms.

Pyrimethanil, component (I), is a fungicide with protective and curativeaction and is used to control grey mould on vines, fruit, vegetables andornamentals. Pyrimethanil (I) is the generic name for4,6-dimethyl-N-phenyl-2-pyrimidinamine, which may be represented by theformula

The components (II) are silver compounds selected from silver acetate,silver alginate, silver azide, silver citrate, silver lactate, silvernitrate, silver perchlorate, silver sulfate, silver chloride, silverthiocyanate, silver-sodium-hydrogen-zirconium phosphate, silversulfadiazine, silver cyclohexanediacetic acid and disilver2,5-dichloro-3,6-dihydroxy-2,5-cyclohexadiene-1,4-dione. Other silvercomponents (II) are products that set silver free using technologies tomake it gradually biologically available such as by ion exchangemechanisms such like using zirconium phosphate based ceramics as areservoir, or silver provided in glass ceramics as reservoir or carrier,or silver provided with zeolites, silica gel or titanium dioxide as areservoir or an inorganic derivative containing silver, incorporatedinto a plastic composition for the preparation of moulded, lacquered orpainted products, such as an amino resin (e.g. urea-formaldehyde resin,melamine formaldehyde resin . . . ) or a thermoplastic (e.g. apolyester, polyethylene, polyacrylate, pvc . . . ), or provided asnano-silver particles typically with a particle size of 1-1000 nm. Saidnano-silver particles may exist either as free particles or as particlesclustered on probiotic bacteria.

The components (II) could as well be presented as a water or solventbased surface modification, a polymer surface coating, a metallicsurface coating or a combination of those technologies.

The antifungal agent pyrimethanil (I) may be present in its free baseform or in the form of an acid addition salt, the latter being obtainedby reaction of the base form with an appropriate acid. Appropriate acidscomprise, for example, inorganic acids, such as the hydrohalic acids,i.e. hydrofluoric, hydrochloric, hydrobromic and hydroiodic, sulfuricacid, nitric acid, phosphoric acid, phosphinic acid and the like; ororganic acids, such as, for example, acetic, propanoic, hydroxyacetic,2-hydroxypropanoic, 2-oxo-propanoic, ethanedioic, propanedioic,butanedioic, (Z)-2-butenedioic, (E)-2-butene-dioic,2-hydroxybutanedioic, 2,3-dihydroxy-butanedioic,2-hydroxy-1,2,3-propane-tricarboxylic, methanesulfonic, ethane-sulfonic,benzenesulfonic, 4-methylbenzene-sulfonic, cyclohexanesulfamic,2-hydroxybenzoic, 4-amino-2-hydroxy-benzoic and the like acids.

The compositions of the present invention have biocidal activity againsta broad range of microorganisms such as bacteria, fungi, yeasts andvirusses. Bacteria include Gram-positive and Gram-negative bacteria.Fungi include e.g. wood-discoloring fungi, wood-destroying fungi, andphytophatogenic fungi. Virusses include HIV, SARS and bird flue.

The biocidal compositions of the present invention are useful in thepreservation of wood, wood products, leather, natural or synthetictextile, fibers, non-wovens, technical textile, plasticized materialsand non-plasticized thermoplastics as polypropylene, polyvinylchloride,etc . . . , paper, wall paper, insulation material, laminates, aminomoulding compounds, paints and coatings, fabrics, floor coverings,synthetic fibres like plasticized polymers, hessian, rope and cordageand biodegradable materials and protect said materials against attackand destruction by bacteria or fungi. As wood or wood products which canbe preserved with the compositions according to the present invention isconsidered, for example, wood products such as timber, lumber, railwaysleepers, telephone poles, fences, wood coverings, wicker-work, windowsand doors, plywood, particle board, waferboards, chipboard, joinery,timber used above ground in exposed environments such as decking andtimber used in ground contact or fresh water or salt water environments,bridges or wood products which are generally used in house building,construction and carpentry. As biodegradable materials besides woodwhich can benefit from treatment with the compositions of the inventioninclude cellulosic material such as cotton.

The biocidal compositions of the present invention are useful in theprevention of microbial contamination or biofilm formation in severalindustrial processes like gaskets, pipes and tubings in contact withfluids or involved in fluid transport, conveyer belts, surfaces andplastic components used in food transport, processing or production, andmedical activities like medical equipment and devices like catheters,pacemakers, implants, surgery equipment and sterile textile.

The biocidal compositions of the present invention are useful in theprevention of hygienic concerns like unwanted bacterial, fungal or algalgrowth on surfaces, safety problems like the presence of Legionella inclosed water systems, Nosocomial infections in hospitals, the presenceof Multi-Resistant Staphylococcus aureus (MRSA), odor problems like infabrics like socks, towels, protective uniforms, shoe linings or infilters or floor coverings. The invention is as well possible to protectareas or items coated with an ultra-hygienic polymer like for themanufacture of electrical devices such as light switches and switchplates; sanitary ware such as toilet seats; and door handles, handrails,baby-changing tables, telephones, and other end-use applications wherethe highest levels of sanitary protection are needed.

The biocidal compositions of the present invention are useful in theprevention of bacterial, fungal or algal growth on surfaces and herewithcausing aesthetical problems for the materials considered

In an embodiment, the present invention relates to a method ofcontrolling microbial growth on wood, wood products and biodegradablematerials, which comprises applying an antimicrobially effective amountof a composition comprising a combination of component (I) and one ormore components (II) in respective proportions to provide a synergisticbiocidal effect, to the wood, wood products, leather, natural orsynthetic textile, fibers, non-wovens, technical textile, plasticizedmaterials and non-plasticized thermoplastics as polypropylene,polyvinylchloride, etc . . . , paper, wall paper, insulation material,laminates, amino moulding compounds, paints and coatings, fabrics, floorcoverings, synthetic fibres like plasticized polymers, hessian, rope andcordage.

The biocidal compositions of the present invention are also useful toprotect engineering materials against microorganisms. Engineeringmaterials which are intended to be protected can be glues, sizes, paintsand plastic articles, cooling lubricants, aqueous hydraulic fluids andother non-living materials which can be infested with, or decomposed by,microorganisms.

In an embodiment, the present invention relates to a method ofcontrolling microbial growth on engineering materials, which comprisesapplying an antimicrobially effective amount of a composition comprisinga combination of component (I) and one or more components (II) inrespective proportions to provide a synergistic biocidal effect, to theengineering materials to be treated.

The biocidal compositions according to the present invention can also beused to protect plants, or parts of plants, e.g. fruit, blossoms,flowers, foliage, stems, roots, cuttings, tubers of plants, fruit andseeds.

As examples of the wide variety of culture plants in which thecombinations of components (I) and (II) according to the presentinvention can be used, there may be named for example cereals, e.g.wheat, barley, rye, oats, rice, sorghum and the like; beets, e.g. sugarbeet and fodder beet; pome and stone fruit and berries, e.g. apples,pears, plums, peaches, almonds, cherries, strawberries, raspberries andblackberries; leguminous plants, e.g. beans, lentils, peas, soy beans;oleaginous plants, e.g. rape, mustard, poppy, olive, sunflower, coconut,castor-oil plant, cocoa, ground-nuts; cucurbitaceae, e.g. pumpkins,gherkins, melons, cucumbers, squashes; fibrous plants, e.g. cotton,flax, hemp, jute; citrus fruit, e.g. orange, lemon, grapefruit,mandarin; vegetables, e.g. spinach, lettuce, asparagus, brassicaceaesuch as cabbages and turnips, carrots, onions, tomatoes, potatoes, hotand sweet peppers; laurel-like plants, e.g. avocado, cinnamon, camphortree; or plants such as maize, tobacco, nuts, coffee, sugar-cane, tea,vines, hops, bananas, rubber plants, as well as ornamental plants, e.g.flowers, shrubs, deciduous trees and evergreen trees such as conifers.This enumeration of culture plants is given with the purpose ofillustrating the invention and not to delimiting it thereto.

In an embodiment, the present invention relates to a method ofcontrolling microbial growth on plants, parts of plants, fruit andseeds, which comprises applying an antimicrobially effective amount of acomposition comprising a combination of component (I) and one or morecomponents (II) in respective proportions to provide a synergisticbiocidal effect, to the plants, parts of plants, fruit and seeds to betreated.

The relative proportions of component (I) and one of the components (II)in compositions comprising a combination of component (I) and one of thecomponents (II) are those proportions which result in a synergisticbiocidal effect, when compared to a composition including, as an activeingredient, either component (I) alone or one of the components (II)alone. As will be understood by those skilled in the art, the saidsynergistic effect may be obtained within various proportions ofcomponents (I) and (II) in the composition, depending on the kind ofmicroorganism towards which effect is measured and the substrate to betreated. Based on the teachings of the present application,determination of the synergistic effect of such combinations can beperformed according to the procedures of the Poison Plate Assay asdescribed in Experiment 1. As a general rule, however, it may be saidthat for most micro-organisms the suitable proportions by weight of theamount of component (I) to component (II) in the active compositionshould lie in the range from 10:1 to 1:10. Particularly, this range isfrom 8:2 to 2:8, more particularly from 3:1 to 1:3 or 2:1 to 1:2.Another particular ratio of component (I) to component (II) in thecompositions of the present invention is a 1:1 ratio between component(I) and one of the components (II).

The quantity of each of the active ingredients in the compositionsaccording to the present invention will be so that a synergisticbiocidal effect is obtained. In particular it is contemplated that theready to use compositions of the present invention comprise component(I) in a range from 10 to 50.000 mg/l. The component (II) is present inan amount ranging from 10 to 50.000 mg/l or mg/kg depending upon thespecific activity of the selected component (II).

The concentration of component (I) and components (II) in the ready touse compositions is also dependent upon the specific conditions whereinthese compositions are used. For instance, in foliar treatment asolution is sprayed directly onto the leaves wherein the concentrationof component (I) ranges from 100 mg to 250 mg/l. Potatoes are treatedwith a composition comprising component (I) in an amount of about 7500mg/l in such a manner that a solution of 2 litres is used for treating1.000 kg. In the treatment of seed the compositions used comprisecomponent (I) in an amount of about 50 g/l in such a manner that 100 kgof seed is treated with a solution of 100 ml to 200 ml. In thepost-harvest treatment of fruit compositions are used comprisingcomponent (I) in an amount ranging from 250 to 500 mg/l in diptreatment, from 500 to 1.000 mg/l in spray treatment, and from 1.000 to2.000 mg/l in wax treatment.

The compositions according to the present invention comprise as acombination of component (I) and component (II) in respectiveproportions to provide a synergistic biocidal effect, and optionally oneor more acceptable carriers.

These carriers are any material or substance with which the compositionof components (I) and (II) is formulated in order to facilitate itsapplication/dissemination to the locus to be treated, for instance bydissolving, dispersing, or diffusing the said composition, and/or tofacilitate its storage, transport or handling without impairing itsantifungal effectiveness. Said acceptable carriers may be a solid or aliquid or a gas which has been compressed to form a liquid, i.e. thecompositions of this invention can suitably be used as concentrates,emulsions, emulsifiable concentrates, oil miscible suspensionconcentrates, oil-miscible liquid, soluble concentrates, solutions,granulates, dusts, sprays, aerosols, pellets, or powders.

In many instances the biocidal compositions to be used directly can beobtained from concentrates, such as e.g. emulsifiable concentrates,suspension concentrates, or soluble concentrates, upon dilution withaqueous or organic media, such concentrates being intended to be coveredby the term composition as used in the definitions of the presentinvention. Such concentrates can be diluted to a ready to use mixture ina spray tank shortly before use. Preferably the compositions of theinvention should contain from about 0.01 to 95% by weight of thecombination of components (I) and (II). More preferably this range isfrom 0.1 to 90% by weight. Most preferably this range is from 1 to 80%by weight, depending on the type of formulation to be selected forspecific application purposes, as further explained in detailshereinafter.

An emulsifiable concentrate is a liquid, homogeneous formulation of thecomponents (I) and (II) to be applied as an emulsion after dilution inwater. A suspension concentrate is a stable suspension of the activeingredients in a fluid intended for dilution with water before use. Asoluble concentrate is a liquid, homogeneous formulation to be appliedas a true solution of the active ingredients after dilution in water.

The fungicidal compositions of the present invention can also beformulated as waxes for use as a cover or coating of e.g. fruit, inparticular citrus fruit.

Biocidal compositions according to the present invention can be of usein post-harvest treatment of fruit, especially citrus fruit. In thelatter instance, the fruit will be sprayed with or dipped or drenchedinto a liquid formulation or the fruit may be coated with a waxycomposition. The latter waxy composition conveniently is prepared bythoroughly mixing a suspension concentrate with a suitable wax. Theformulations for spray, dip or drench applications may be prepared upondilution of a concentrate such as, e.g. an emulsifiable concentrate, asuspension concentrate or a soluble liquid, with an aqueous medium. Suchconcentrate in most instances consists of the active ingredients, adispersing or suspending agent (surfactant), a thickening agent, a smallamount of organic solvent, a wetting agent, optionally some anti-freezeagent, and water.

The biocidal compositions of the present invention can also be used forprotecting seed against fungi. To that effect the present fungicidalcompositions can be coated on seed, in which case the seed grains aredrenched consecutively with a liquid composition of the activeingredients or if they are coated with a previously combinedcomposition. The compositions can also be sprayed or atomised onto theseed using e.g. a spinning disc atomiser.

The combination of components (I) and (II) is preferably applied in theform of compositions wherein both said components are intimately admixedin order to ensure simultaneous administration to the materials to beprotected. Administration or application of both components (I) and (II)can also be a “sequential-combined” administration or application, i.e.component (I) and component (II) are administered or appliedalternatively or sequentially in the same place in such a way that theywill necessarily become admixed together at the locus to be treated.This will be achieved namely if sequential administration or applicationtakes place within a short period of time e.g. within less than 24hours, preferably less than 12 hours. This alternative method can becarried out for instance by using a suitable single package comprisingat least one container filled with a formulation comprising the activecomponent (I) and at least one container filled with a formulationcomprising an active component (II). Therefore the present inventionalso encompasses a product containing:

(a) a composition comprising component (I) (i.e. pyrimethanil) and

(b) a composition comprising a component (II), selected from silveracetate, silver alginate, silver azide, silver citrate, silver lactate,silver nitrate, silver perchlorate, silver sulfate, silver chloride,silver thiocyanate, silver-sodium-hydrogen-zirconium phosphate, silversulfadiazine, silver cyclohexanediacetic acid and disilver2,5-dichloro-3,6-dihydroxy-2,5-cyclohexadiene-1,4-dione; as acombination for simultaneous or sequential use, wherein saidcompositions (a) and (b) are in respective proportions to provide asynergistic biocidal effect. Other suitable silver components (II) areproducts that set silver free using technologies to make it graduallybiologically available such as by ion exchange mechanisms such likeusing zirconium phosphate based ceramics as a reservoir, or silverprovided in glass ceramics as reservoir or carrier, or silver providedwith zeolites, silica gel or titanium dioxide as a reservoir or aninorganic derivative containing silver, incorporated into a plasticcomposition for the preparation of moulded, lacquered or paintedproducts, such as an amino resin (e.g. urea-formaldehyde resin, melamineformaldehyde resin . . . ) or a thermoplastic (e.g. a polyester,polyethylene, polyacrylate, pvc . . . ), or provided as nano-silverparticles typically with a particle size of 1-1000 nm. Such products mayconsist of a suitable package comprising separate containers whereineach container comprises component (I) or one of the components (II),preferably in formulated form. Such formulated forms in general have thesame composition as described for the formulations containing bothactive ingredients.

Appropriate carriers and adjuvants for use in the compositions of thepresent invention may be solid or liquid and correspond to suitablesubstances known in the art of formulation, such as, for example naturalor regenerated mineral substances, solvents, dispersants, surfactants,wetting agents, adhesives, thickeners, binders, fertilizers oranti-freeze agents.

Apart from both the aforementioned components (I) and (II), thecompositions according to the present invention may further compriseother active ingredients, e.g. other microbiocides, in particularfungicides, and also insecticides, acaricides, nematicides, herbicides,plant growth regulators and fertilizers.

The components (I) and (II) are used in unmodified form or, preferably,together with the adjuvants conventionally employed in the art offormulation. They are therefore formulated following art-knownprocedures to emulsifiable concentrates, directly sprayable or dilutablesolutions, dilute emulsions, wettable powders, soluble powders, dusts,granulates, and also encapsulations in e.g. polymer substances. As withthe nature of the compositions, the methods of application, such asspraying, atomizing, dusting, scattering or pouring, are chosen inaccordance with the intended objectives and the prevailingcircumstances.

The formulations, i.e. the compositions, preparations or mixturescomprising the active ingredients and, where appropriate, a solid orliquid adjuvant, are prepared in known manner, e.g. by homogeneouslymixing and/or grinding the active ingredients with extenders, e.g.solvents, solid carriers and, where appropriate, surface-activecompounds (surfactants).

Suitable solvents are aromatic hydrocarbons, preferably the fractionscontaining 8 to 12 carbon atoms, e.g. dimethylbenzene mixtures orsubstituted naphthalenes, phthalates such as dibutyl phthalate ordioctyl phthalate, aliphatic or alicyclic hydrocarbons such ascyclohexane or paraffins, alcohols and glycols and their ethers andesters, such as ethanol, ethylene glycol, ethylene glycol monomethyl ormonoethyl ether, ketones such as cyclohexanone, strongly polar solventssuch as N-methyl-2-pyrrolidone, dimethylsulfoxide or dimethylformamide,as well as vegetable oils or epoxidised vegetable oils such asepoxidised coconut oil or soybean oil; or water.

The solid carriers used e.g. for dusts and dispersible powders arenormally natural mineral fillers such as calcite, talcum, kaolin,montmorillonite or attapulgite. In order to improve the physicalproperties it is also possible to add highly dispersed silicic acid orhighly dispersed absorbent polymers. Suitable granulated absorbentcarriers are of the porous type, for example pumice, broken brick,sepiolite or bentonite; and suitable nonsorbent carriers are materialssuch as calcite or sand. In addition, a great number of pregranulatedmaterials of inorganic or organic nature can be used, e.g. especiallydolomite or pulverised plant residues.

Suitable surface-active compounds to be used in the compositions of thepresent invention are non-ionic, cationic and/or anionic surfactantshaving good emulsifying, dispersing and wetting properties. The term“surfactants” will also be understood as comprising mixtures ofsurfactants.

Appropriate carriers and adjuvants for use in the compositions of thepresent invention may be solid or liquid and correspond to suitablesubstances known in the art for preparing formulations for treatingplants or their loci, or for treating plant products, in particular fortreating wood, such as, for example, natural or regenerated mineralsubstances, solvents, dispersants, surfactants, wetting agents,adhesives, thickeners, binders, fertilizers, anti-freeze agents,repellents, colour additives, corrosion inhibitors, water-repellingagents, siccatives, UV-stabilizers and other active ingredients.

Suitable anionic surfactants can be both water-soluble soaps andwater-soluble synthetic surface-active compounds.

Suitable soaps are the alkali metal salts, earth alkaline metal salts orunsubstituted or substituted ammonium salts of higher fatty acids(C₁₀-C₂₂), e.g. the sodium or potassium salts of oleic or stearic acid,or of natural fatty acid mixtures which can be obtained e.g. fromcoconut oil or tallow oil. In addition, there may also be mentionedfatty acid methyltaurin salts.

More frequently, however, so-called synthetic surfactants are used,especially fatty sulfonates, fatty sulfates, sulfonated benzimidazolederivatives or alkylarylsulfonates. The fatty sulfonates or sulfates areusually in the form of alkali metal salts, earth alkaline metal salts orunsubstituted or substituted ammonium salts and contain an alkyl radicalhaving from 8 to 22 carbon atoms said alkyl also comprising radicalsderived from acyl radicals, e.g. the sodium or calcium salt oflignosulfonic acid, of dodecylsulfate or of a mixture of fatty alcoholsulfates obtained from natural fatty acids. These compounds alsocomprise the salts of sulfuric acid esters and sulfonic acids of fattyalcohol/ethylene oxide adducts. The sulfonated benzimidazole derivativespreferably contain 2 sulfonic acid groups and one fatty acid radicalcontaining 8 to 22 carbon atoms. Examples of alkylarylsulfonates are thesodium, calcium or triethanolamine salts of dodecylbenzene sulfonicacid, dibutylnaphthalene-sulfonic acid, or of a naphthalene-sulfonicacid/formaldehyde condensation product. Also suitable are correspondingphosphates, e.g. salts of the phosphoric acid ester of an adduct ofp-nonylphenol with 4 to 14 moles of ethylene oxide, or phospholipids.

Non-ionic surfactants are preferably polyglycol ether derivatives ofaliphatic or cycloaliphatic alcohols, or saturated or unsaturated fattyacids and alkylphenols, said derivatives containing 3 to 10 glycol ethergroups and 8 to 20 carbon atoms in the (aliphatic) hydrocarbon moietyand 6 to 18 carbon atoms in the alkyl moiety of the alkylphenols.

Further suitable non-ionic surfactants are the water-soluble adducts ofpolyethylene oxide with polypropylene glycol,ethylenediaminopoly-propylene glycol containing 1 to 10 carbon atoms inthe alkyl chain, which adducts contain 20 to 250 ethylene glycol ethergroups and 10 to 100 propylene glycol ether groups. These compoundsusually contain 1 to 5 ethylene glycol units per propylene glycol unit.

Representative examples of non-ionic surfactants arenonylpheno-lpolyethoxy ethanols, castor oil polyglycol ethers,polypropylene/polyethylene oxide adducts,tributylphenoxypolyethoxyethanol, polyethylene glycol andoctylphenoxypolyethoxy-ethanol. Fatty acid esters of polyethylenesorbitan, such as polyoxyethylene sorbitan trioleate, are also suitablenon-ionic surfactants.

Particularly advantageous additives useful to improve the applicationand reduce the dose of the active ingredients, are the natural (animalor plant) or synthetic phospholipids of the cephalin or lecithin typesuch as, for example, phosphatidyl-ethanolamine, phosphatidylserine,phosphatidylglycerine, lysolecithin, or cardiolipin. Such phospholipidsmay be obtained from animal or plant cells, in particular from brain-,heart- or liver tissue, egg yolks or soy beans. Appropriate suchphospholipids are for instance, phosphatidylchlorin mixtures. Syntheticphospholipids are for instance, dioctanylphosphatidyl-chloline anddipalmitoylphosphatidylcholine.

Experimental Part Experiment 1: Poison Plate Assay

-   Name of the primary compound:—pyrimethanil (I)-   Name of the silver salt:—silver nitrate or silver perchlorate-   Stock solution: 1000 ppm in DMSO-   Test combinations:

% product A + % product B 100 + 0 80 + 20 66 + 33 50 + 50 33 + 66 20 +80 0 + 100

-   Concentrations of total active ingredient in the combinations:-   a first series of concentrations increasing with steps of ⅓:    2.11-2.82-3.75-5.01-6.67-8.90-11.87-15.82-21.09-28.13-37.50-50.00    ppm-   a second series of concentrations increasing with steps of ⅓:    21.12-28.16-37.54-50.06-66.74-88.99-118.65-158.20-210.94-281.25-375.00-500.00    ppm-   Culture medium: Bacteria: Tryptose Agar (TA): 20 g bacto tryptose, 5    g sodium chloride, 1 g bacto dextrose and 15 g bacto agar in I liter    deionised water    -   Fungi and yeast: Glucose Agar (GA): 10 g glucose, 1.5 g K2HPO4,        2 g KH2PO4, 1 g (NH4)2SO4, 0.5 g MgSO₄ and 12.5 g agar in 1        liter deionised water-   Experimental set up: 24-well plates-   Test species:

Bacteria Pseudomonas aeruginosa NCIB 8295 Escherichia coli SSB I 8Staphylococcus aureus LMG 8064 Fungi and yeast Aspergillus versicolorCNCM 1187-79 Penicillium purpurogenum CBS 170.60 Rhodoturula rubra B52183 Stachybotris chartarum CBS 328.37 Ulocladium atrum IMI 214669aTrichoderma longibrachiatum ATCC 13631

-   Inoculum: with a spore/mycelium suspension (2 μl) or a small piece    of agar from the margin of an actively growing colony-   Culture conditions: Bacteria: 27° C., 70% relative humidity, dark.    Fungi: 22° C., 70% relative humidity, dark-   Evaluation: Evaluation after one week for bacteria and two weeks for    fungi    MIC values (minimum inhibitory concentration in ppm total active    ingredient) were noted and synergy was calculated using the Synergy    Index method described by Kull et al. (Kull, F. C., P. C.    Eismann, H. D. Sylvestrowicz, and R. L. Mayer (1961) “Mixtures of    quaternary ammonium compounds and long-chain fatty acids as    antifungal agents” Applied Microbiology 9: 538-541; also see Zwart    Voorspuij, A. J., and C. A. G. Nass (1957) “Some aspects of the    notions additivity, synergism and antagonism in the simultaneous    activity of two antibacterial agents in vitro” Arch. intern.    Pharmacodynamie 109: 211-228; Steinberg, D. C. (2000) “Measuring    synergy” cosmetics & Toiletries 115(11): 59-62; and Lada, A., A. N.    Petrocci, H. A. Green, and J. J. Merianos (1977) “Antimicrobial    composition” U.S. Pat. No. 4,061,750, 3 pp.):

${{Synergy}\mspace{14mu} {Index}\mspace{14mu} \left( {S\; I} \right)} = {\frac{Q_{a}}{Q_{A}} + \frac{Q_{b}}{Q_{B}}}$

wherein:

-   -   Q_(A) is the concentration of compound A in ppm, acting alone,        which produced an end point (e.g. MIC),    -   Q_(a) is the concentration of compound A in ppm, in the mixture,        which produced an end point (e.g. MIC),    -   Q_(B) is the concentration of compound B in ppm, acting alone,        which produced an end point (e.g. MIC),    -   Q_(b) is the concentration of compound B in ppm, in the mixture,        which produced an end point (e.g. MIC).        When the Synergy Index is greater than 1.0, antagonism is        indicated. When the SI is equal to 1.0, additivity is indicated.        When the SI is less than 1.0, synergism is demonstrated.

TABLE 1 MIC-values (minimum inhibitory concentration in ppm) and synergyindex of combinations of pyrimethanil with silver nitrate %pyrimethanil + MIC-values Synergy % silver nitrate in ppm IndexEscherichia coli 100 + 0  666.67 — 80 + 20 210.94 0.88 66 + 33 118.650.71 50 + 50 88.99 0.73 33 + 66 66.67 0.70 20 + 80 66.67 0.82 0 + 10066.67 — Aspergillus versicolor 100 + 0  666.67 — 80 + 20 210.94 0.6166 + 33 210.94 0.80 50 + 50 158.20 0.78 33 + 66 88.99 0.54 20 + 80 88.990.62  0 + 100 118.65 — Rhodoturula rubra 100 + 0  281.25 — 80 + 20158.20 0.72 66 + 33 158.20 0.82 50 + 50 118.65 0.71 33 + 66 118.65 0.8120 + 80 118.65 0.88  0 + 100 118.65 —

TABLE 2 MIC-values (minimum inhibitory concentration in ppm) and synergyindex of combinations of pyrimethanil with silver perchlorate %pyrimethanil + MIC-values Synergy % silver perchlorate in ppm IndexEscherichia coli 100 + 0  666.67 — 80 + 20 210.94 0.88 66 + 33 118.650.71 50 + 50 118.65 0.98 33 + 66 66.67 0.70 20 + 80 66.67 0.82  0 + 10066.67 — Aspergillus versicolor 100 + 0  375.00 — 80 + 20 158.20 0.6966 + 33 88.99 0.49 50 + 50 88.99 0.62 33 + 66 88.99 0.75 20 + 80 66.670.64  0 + 100 88.99 — Rhodoturula rubra 100 + 0  281.25 — 80 + 20 118.650.69 66 + 33 88.99 0.65 50 + 50 88.99 0.82 33 + 66 88.99 0.99 20 + 8066.67 0.85  0 + 100 66.67 —

Experiment 2: Poison Plate Assay

-   Name of the primary compound:—pyrimethanil (I)-   Name of the silver salt: Microsil™ from Avecom (Bloemendalestraat    138, 8730 Beernem, Belgium)-   Microsil™ is a suspension of colloidal silver metal particles,    produced by and clustered on probiotic bacteria. The diameter of the    silver particles varies between 3 to 20 nm. The oxidation state of    the silver in Microsil™ is 0 (Ag⁰).-   Microsil™ is produced as a suspension of finely dispersed colloidal    Ag⁰ particles, stabilized on a biological carrier molecule, in    water. The probiotic carrier exists only as a non-viable and    stabilizing biocomponent.-   Stock solution: 1000 ppm in DMSO-   Test combinations:

% product A + % product B 100 + 0 80 + 20 66 + 33 50 + 50 33 + 66 20 +80 0 + 100

-   Concentrations: 50-37.5-28.1-21.1-15.8-11.9-8.9-6.7-5.0-3.8-2.8-2.1    ppm-   Culture medium: Bacteria: Tryptose Agar (TA): 20 g bacto tryptose, 5    g sodium chloride, 1 g bacto dextrose and 15 g bacto agar in I liter    deionised water-   Experimental set up: 24-well plates-   Test species:

Bacteria Streptomyces griseus (g+) LMG 19302

-   Inoculum: the nutrient medium is inoculated by adding 10 μl of an    actively growing liquid culture of the test bacteria in tryptose    broth (without agar)-   Culture conditions: Bacteria: 27° C., 70% relative humidity, dark.-   Evaluation: Evaluation after 5 days    MIC values (minimum inhibitory concentration in ppm total active    ingredient) were noted and synergy was calculated using the Synergy    Index method described above.

TABLE 3 MIC-values (minimum inhibitory concentration in ppm) and synergyindex of combinations of pyrimethanil with Microsil™ % pyrimethanil +MIC-values Synergy % Microsil™ in ppm Index Streptomyces griseus 100 +0  66.7 — (g+) 80 + 20 50.0 0.80 66 + 33 50.0 0.83 50 + 50 37.5 0.6533 + 66 28.1 0.51 20 + 80 28.1 0.53  0 + 100 50.0 —

1. A composition comprising a combination of pyrimethanil or a saltthereof, as component (I), and as a component (II) a silver compoundselected from silver acetate, silver alginate, silver azide, silvercitrate, silver lactate, silver nitrate, silver perchlorate, silversulfate, silver chloride, silver thiocyanate,silver-sodium-hydrogen-zirconium phosphate, silver sulfadiazine, silvercyclohexanediacetic acid and disilver2,5-dichloro-3,6-dihydroxy-2,5-cyclohexadiene-1,4-dione; wherebycomponent (I) and one of the components (II) are in respectiveproportions to provide a synergistic biocidal effect.
 2. A compositionas claimed in claim 1 wherein component (II) is silver nitrate or silverperchlorate.
 3. A composition comprising a combination of pyrimethanilor a salt thereof, as component (I), and as a component (II) a productthat sets silver free using technologies to make it graduallybiologically available whereby component (I) and one of the components(II) are in respective proportions to provide a synergistic biocidaleffect.
 4. A composition as claimed in claim 1 wherein the ratio byweight of component (I) to component (II) ranges from 10:1 to 1:10.
 5. Acomposition as claimed in claim 1 wherein the amount of component (I) ispresent in a range from 10 to 50.000 mg/l and the amount of component(II) is present in a range from 10 to 50.000 mg/l.
 6. A method ofcontrolling microbial growth on wood, wood products and biodegrablematerials, which comprises applying an antimicrobially effective amountof a composition as claimed in claim 1, to the wood, wood products andbiodegrable materials to be treated.
 7. A method of controllingmicrobial growth on engineering materials, which comprises applying anantimicrobially effective amount of a composition as claimed in claim 1,to the engineering materials to be treated.
 8. (canceled)
 9. A productcontaining (a) a composition comprising component (I), pyrimethanil; and(b) a composition comprising a component (II) selected from silveracetate, silver alginate, silver azide, silver citrate, silver lactate,silver nitrate, silver perchlorate, silver sulfate, silver chloride,silver thiocyanate, silver-sodium-hydrogen-zirconium phosphate, silversulfadiazine, silver cyclohexanediacetic acid and disilver2,5-dichloro-3,6-dihydroxy-2,5-cyclohexadiene-1,4-dione, as acombination for simultaneous or sequential use, wherein saidcompositions (a) and (b) are in respective proportions to provide asynergistic biocidal effect.
 10. A product containing (a) a compositioncomprising component (I), pyrimethanil; and (b) a composition comprisinga component (II) selected from a product that sets silver free usingtechnologies to make it gradually biologically available, as acombination for simultaneous or sequential use, wherein saidcompositions (a) and (b) are in respective proportions such as toprovide a synergistic biocidal effect.
 11. The composition of claim 3,wherein the technology is ion exchange mechanisms or provided asnano-silver particles either as free particles or as particles clusteredon probiotic bacteria.
 12. The composition of claim 3, wherein thetechnology is zirconium phosphate based ceramics as a reservoir, orsilver provided in glass ceramics as reservoir or carrier, or silverprovided with zeolites, silica gel or titanium dioxide as a reservoir oran inorganic derivative containing silver, incorporated into a plasticcomposition for the preparation of moulded, lacquered or paintedproducts.
 13. The product of claim 10, wherein the technology is ionexchange mechanisms or provided as nano-silver particles either as freeparticles or as particles clustered on probiotic bacteria.
 14. Theproduct of claim 10, wherein the technology is zirconium phosphate basedceramics as a reservoir, or silver provided in glass ceramics asreservoir or carrier, or silver provided with zeolites, silica gel ortitanium dioxide as a reservoir or an inorganic derivative containingsilver, incorporated into a plastic composition for the preparation ofmoulded, lacquered or painted products.